FI81576B - Foerfarande foer framstaellning av derivat av 6-(1-hydroxietyl)-2-(1,2-disubstituerade-4-pyrrolidinyltio)-2- karbapenem-3-karboxylsyra, vilka aer anvaendbara som laekemedel. - Google Patents
Foerfarande foer framstaellning av derivat av 6-(1-hydroxietyl)-2-(1,2-disubstituerade-4-pyrrolidinyltio)-2- karbapenem-3-karboxylsyra, vilka aer anvaendbara som laekemedel. Download PDFInfo
- Publication number
- FI81576B FI81576B FI855128A FI855128A FI81576B FI 81576 B FI81576 B FI 81576B FI 855128 A FI855128 A FI 855128A FI 855128 A FI855128 A FI 855128A FI 81576 B FI81576 B FI 81576B
- Authority
- FI
- Finland
- Prior art keywords
- group
- compound
- formula
- hydroxyethyl
- carbapenem
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 183
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 8
- -1 1,2-disubstituted-4-pyrrolidinylthio Chemical group 0.000 claims description 90
- 238000006243 chemical reaction Methods 0.000 claims description 68
- 150000002148 esters Chemical class 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000006239 protecting group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
- 239000007858 starting material Substances 0.000 claims description 13
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical group O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000004986 diarylamino group Chemical group 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 239000011574 phosphorus Substances 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 28
- 125000000217 alkyl group Chemical group 0.000 abstract description 14
- 231100000417 nephrotoxicity Toxicity 0.000 abstract description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 239000001257 hydrogen Substances 0.000 abstract description 5
- 230000003115 biocidal effect Effects 0.000 abstract description 3
- 125000000547 substituted alkyl group Chemical group 0.000 abstract description 3
- 150000002431 hydrogen Chemical class 0.000 abstract 1
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- 239000000047 product Substances 0.000 description 24
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- 238000000862 absorption spectrum Methods 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 19
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- 239000000243 solution Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000002253 acid Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 125000001424 substituent group Chemical group 0.000 description 14
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical class C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 241000283973 Oryctolagus cuniculus Species 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 125000003710 aryl alkyl group Chemical group 0.000 description 8
- 238000004821 distillation Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 229940126062 Compound A Drugs 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 4
- 231100000989 no adverse effect Toxicity 0.000 description 4
- 239000008055 phosphate buffer solution Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 3
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- 125000004423 acyloxy group Chemical group 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000007086 side reaction Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/16—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 3
- C07D477/20—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
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- Communicable Diseases (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Lubricants (AREA)
- Steroid Compounds (AREA)
- Indole Compounds (AREA)
Claims (10)
1. Förfarande för framställning av 6-(l-hydroxietyl)-2-(l,2-disubsti-tuerade-4-pyrrolidinyltio)-2-karbapenem-3-karboxylsyraderivat enligt 5 formeln (I), vilka är användbara som läkemedel: 10 fl' 2 OH I f | % «) i. H3C/C\-- NH J-H-k
0 CO OH 20 där: avser en hydroximetyl-, Cj-C^-alkanoyloxi-C^-C^-alkyl-, en C^-C^- 4 5 25 alkoxikarbonylgrupp, eller en grupp med formeln -CONR R dar 4 5 R och R är likadana eller olika och vardera avser en väteatom eller en Cj-C^-alkylgrupp; 2 30. avser en väteatom, en C^-C^-alkyl- eller en C^-C^-alkoxi-C^-C^-alkyl-grupp; och farmaceutiskt acceptable salter och estrar av dessa, 35 kännetecknat därav, att förfarandet innefattar: 57 8 1 5 7 6 1 (a) att man bringar en förening med formeln (III):
1 Patentkrav
2. Förfarande enligt patentkrav 1, kännetecknat därav, att utglngsämnena och reaktionsförhallandena väljs för att framställa: (5R,6S)-6-/1(R)-hydroxietyl/-2-(2-karbamoyl-l-acetimidoylpyrrolidin-4-35 yltio)-2-karbapenem-3-karboxylsyra eller farmaceutlskt acceptabla salter eller estrar av denna. ., 81576
3. FBrfarande enligt patentkrav 1, kännetecknat därav, att utgangsämnena och reaktionsfBrhillandena väljs för att framställa: (5R,6S)-6-/I (R)-hydroxietyl/-2-(2-karbamoyl-l-(ot-metoxiacetimidoyl)-pyrrolidin-4-yltio)-2-karbapenem-3-karboxylsyra eller faraaceutiskt g acceptabla salter eller estrar av denna.
4. FBrfarande enligt patentkrav 1, kännetecknat därav, att utgangsämnena och reaktionsfBrhillandena väljs för att framställa: (5R,6S)-6-/l (R)-hydroxietyl7-2-(2-N-metylkarbamoyl-l-acetimidoyl- jQ pyrrolldin-4-yltio)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptabla salter eller estrar av denna.
5. FBrfarande enligt patentkrav 1, kännetecknat därav, att utgangsämnena och reaktionsfBrhillandena väljs för att framställa: 15 (5R,6_S)-6-/l(R)-hydroxietyl7-2-(2-N,N-dimetylkarbamoyl-l-acetimidoyl- pyrrolidin-4-yltio)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptabla salter eller estrar av denna.
5 RII HjC^ ]- j (m)
10. N COOR7 15 7 8 (där R avser en skyddande grupp, R avser en alkansulfonylgrupp, en aryleulfonylgrupp, en dialkylfoeforylgrupp eller en diarylfosforylgrupp och R^ avser en hydroxigrupp eller en skyddad hydroxigrupp) att reagera med en förening med formeln (IV) 20 7 - Ύν'Γ . 30 1 * 2 (där R är nagon av de grupper som representeras av R , eller en skyddad hydroximetylgrupp, och R^ avser en skyddande grupp eller 2 3' 2 en grupp med formeln -C(R )*NR där R är definierad som ovan och 3» g
35 R är en skyddande grupp), avlägsnar de skyddande grupperna R eller 3' R för att fä en förening med formeln (V): 58 81 576 5 m* R1' -R6 I , f | 10 -- H3C -1 J-H-L r coor7 15 20 (där R1 ,R7 och R1* är definierade som ovan) och R8 avser en väteatom 2 3.2 3 eller en grupp med foraeln -C(R )=NR där R och R är definierade g ? som ovan, och dl R är en väteatom, bringas nämnda förening med foraeln (V) att reagera med en förening med foraeln (VI): 25 r9o-c(r2)«nr3' (VI) 2 3' 9 (där R och R är definierade som ovan och R avser en väteatom eller en C^-C^-alkylgrupp; eller med ett reaktivt derivat av denna, för att f! en förening med foraeln (Va): 30 35 59 81576 5 RV 7 R" Λ-c^ iu eli %-R3 j° * y-fY— J—*—
0 XOQR7 (Vai 15 1» 2 3' 7 11 20 (där R , R , R , R och R är definierade som ovan); eller (b) man brlngar en förening med formeln (VII) 25 n· fln i I H6 /CH -s-1_I 30 ¥ >—xc^ I I II (vii) 0^-^C=Q ° CM*7 «O 81576 1 (där R* , R^ och R^ är definierade som ovan, att reagera med en fosfor-förening med formeln: P«10)3 5 (där R^ aveer en alkoxigrupp, en aralkyloxigrupp, en dialkylaminogrupp eller en diarylaminogrupp) för att fa en förening med formeln (VIII) 10 J" ^«-«6 HjC^S-- '
15 J-O <mt>
0 C=P(RlO)3 . CQOR7 20 (där R^ , R^,R^,R^ och R^ är definierade som ovan), upphettnlng av nämnda förening med formeln (VIII) för att förorsaka ringtillslutning 6 3» av azetidinonringen, och avlägsna de skyddande grupperna R och R och dl den resulterande föreningen har formeln (V) brlngas den att 25 reagera med en förening med formeln (VI) som definierades ovan, (c) vid behov avlägsnar de skyddande grupperna i vilket lärapligt skede som heist; och 30 (d) valbart saltbildning och/eller förestring av föreningen.
6. FBrfarande enligt patentkrav 1, kännetecknat därav, 20 ett utgangsämnena och reaktionsfBrhillandena väljs fBr att framställa: (5R,6£>)-6-^1 (Ip-hydroxietyl/^-^-N-metoxikarbamoyl-l-acetimidoyl-pyrrolidin^-yltioJ^-karbapenem-S-karboxylsyra eller farmaceutiskt acceptabla salter eller estrar av denna.
7. FBrfarande enligt patentkrav 1, kännetecknat därav, att utgangsämnena och reaktionsfBrhillandena väljs för att framställa: (5R,6S)-6-^i (R)-hydroxietyl7-2-(2-metoxikarbonyl-l-acetimidoyl-pyrrolidin-4-yltio)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptabla salter eller estrar av denna. 30
8. FBrfarande enligt patentkrav 1, kännetecknat därav, att utglngsämnena och reaktionsfBrhillandena väljs för att framställa: (5R,6S)-6-^i(R)-hydroxlety^“2-(2-hydroximetyl-l-acetimidoylpyrrolidin-4-yltio)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptabla 35 salter eller estrar av denna. 62 8 1 5 7 6 1
9. Förfarande enligt patentkrav 1, kännetecknat därav, ate utgängsämnena och reaktionsförhallandena väljs för att framställa: (5R,6S)-6-/l(R)-hydroxietyl/-2-(2-acetoximety1-1-acetimidoylpyrrolldin-4-yltio)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptable 5 salter eller estrar av denna.
10. Förfarande enligt patentkrav 1, kännetecknat därav, att utglngsämnena och reaktionsförhallandena väljs för att framställa: (5R,6S)-6-/l(R)-hydroxietyl7-2-(2-karbamoyloximetyl-l-acetimidoyl-1 q pyrrolldin-4-yltlo)-2-karbapenem-3-karboxylsyra eller farmaceutiskt acceptable salter eller estrar av denna. 15 20 25 30 35 II
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28170084 | 1984-12-25 | ||
| JP28170084 | 1984-12-25 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI855128A0 FI855128A0 (fi) | 1985-12-20 |
| FI855128A FI855128A (fi) | 1986-06-26 |
| FI81576B true FI81576B (fi) | 1990-07-31 |
| FI81576C FI81576C (sv) | 1990-11-12 |
Family
ID=17642759
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI855128A FI81576C (sv) | 1984-12-25 | 1985-12-20 | Förfarande för framställning av derivat av 6-(1-hydroxietyl)-2-(1,2-di substituerade-4-pyrrolidinyltio)-2-karbapenem-3-karbokxylsyra, vilka ä r användbara som läkemedel |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US4740507A (sv) |
| EP (1) | EP0186525B1 (sv) |
| JP (1) | JPS61275279A (sv) |
| KR (1) | KR930005332B1 (sv) |
| CN (1) | CN1014246B (sv) |
| AT (1) | ATE51624T1 (sv) |
| AU (1) | AU575232B2 (sv) |
| CA (1) | CA1254562A (sv) |
| DE (1) | DE3576957D1 (sv) |
| DK (1) | DK169384B1 (sv) |
| ES (2) | ES8706148A1 (sv) |
| FI (1) | FI81576C (sv) |
| HU (1) | HU196071B (sv) |
| IE (1) | IE58823B1 (sv) |
| NO (1) | NO163957C (sv) |
| NZ (1) | NZ214676A (sv) |
| PH (1) | PH25391A (sv) |
| ZA (1) | ZA859797B (sv) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60202886A (ja) * | 1984-03-27 | 1985-10-14 | Sankyo Co Ltd | １―置換カルバペネム―３―カルボン酸誘導体 |
| JPS6426580A (en) * | 1987-07-21 | 1989-01-27 | Sankyo Co | Production of carbapenem derivative |
| US5102877A (en) * | 1989-04-28 | 1992-04-07 | Fujisawa Pharmaceutical Co., Ltd. | 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds |
| US5286721A (en) * | 1990-10-15 | 1994-02-15 | Fujisawa Pharmaceutical Co., Ltd. | 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid compounds |
| TW209220B (sv) * | 1991-11-27 | 1993-07-11 | Manyu Seiyaku Kk | |
| GB9202298D0 (en) | 1992-02-04 | 1992-03-18 | Ici Plc | Antibiotic compounds |
| GB9210096D0 (en) * | 1992-05-11 | 1992-06-24 | Fujisawa Pharmaceutical Co | 1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic acid derivatives and their preparation |
| JP2696807B2 (ja) * | 1992-08-06 | 1998-01-14 | 田辺製薬株式会社 | カルバペネム誘導体の製法 |
| HUP0000952A3 (en) * | 1997-02-07 | 2000-12-28 | Kyoto Pharma Ind | Carbapenem compounds, process for their preparation and pharmaceutical compositions containing them |
| AU760386B2 (en) | 1998-05-01 | 2003-05-15 | Kyoto Pharmaceutical Industries, Ltd. | Carbapenem derivatives, utilization thereof and intermediate compounds of the same |
| HUP0400444A3 (en) * | 2001-05-21 | 2007-02-28 | Kyoto Pharmaceutical Ind | Carbapenem compound, pharmaceutical compositions containing them and their use |
| GB0400382D0 (en) * | 2004-01-09 | 2004-02-11 | Glaxo Group Ltd | Novel processes |
| US7932381B2 (en) * | 2005-02-15 | 2011-04-26 | Shionogi & Co., Ltd. | Process for producing carbapenem derivative and intermediate crystal therefor |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4383946A (en) * | 1980-03-27 | 1983-05-17 | Merck & Co., Inc. | Process for the preparation of 1-carbapenems and intermediates via silyl-substituted dithioacetals |
| US4552873A (en) * | 1981-08-19 | 1985-11-12 | Sankyo Company Limited | Carbapenem compounds, and compositions containing them |
| JPS5913757A (ja) * | 1982-07-14 | 1984-01-24 | Sankyo Co Ltd | ３−メルカプトピロリジン誘導体及びその製法 |
| JPS5916892A (ja) * | 1982-07-19 | 1984-01-28 | Sankyo Co Ltd | カルバペネム−３−カルボン酸誘導体およびその製法 |
| JPS59205379A (ja) * | 1983-05-09 | 1984-11-20 | Sumitomo Chem Co Ltd | 新規なβ−ラクタム化合物及びその製造法 |
| CA1283906C (en) * | 1983-05-09 | 1991-05-07 | Makoto Sunagawa | .beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF |
-
1985
- 1985-12-20 FI FI855128A patent/FI81576C/sv not_active IP Right Cessation
- 1985-12-20 JP JP60285663A patent/JPS61275279A/ja active Pending
- 1985-12-23 ZA ZA859797A patent/ZA859797B/xx unknown
- 1985-12-23 NO NO855241A patent/NO163957C/no unknown
- 1985-12-23 US US06/812,344 patent/US4740507A/en not_active Expired - Fee Related
- 1985-12-23 HU HU854957A patent/HU196071B/hu not_active IP Right Cessation
- 1985-12-23 NZ NZ214676A patent/NZ214676A/xx unknown
- 1985-12-23 CN CN85109699A patent/CN1014246B/zh not_active Expired
- 1985-12-23 DK DK604485A patent/DK169384B1/da active
- 1985-12-23 IE IE330085A patent/IE58823B1/en not_active IP Right Cessation
- 1985-12-24 ES ES550403A patent/ES8706148A1/es not_active Expired
- 1985-12-24 CA CA000498605A patent/CA1254562A/en not_active Expired
- 1985-12-24 AU AU51699/85A patent/AU575232B2/en not_active Ceased
- 1985-12-24 KR KR1019850009792A patent/KR930005332B1/ko not_active IP Right Cessation
- 1985-12-24 PH PH33239A patent/PH25391A/en unknown
- 1985-12-30 EP EP85309537A patent/EP0186525B1/en not_active Expired - Lifetime
- 1985-12-30 AT AT85309537T patent/ATE51624T1/de not_active IP Right Cessation
- 1985-12-30 DE DE8585309537T patent/DE3576957D1/de not_active Expired - Fee Related
-
1986
- 1986-08-22 ES ES557035A patent/ES8707535A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| HU196071B (en) | 1988-09-28 |
| CA1254562A (en) | 1989-05-23 |
| ES557035A0 (es) | 1987-08-01 |
| ZA859797B (en) | 1986-09-24 |
| IE853300L (en) | 1986-06-25 |
| DK169384B1 (da) | 1994-10-17 |
| CN1014246B (zh) | 1991-10-09 |
| NO163957B (no) | 1990-05-07 |
| CN85109699A (zh) | 1986-08-13 |
| ATE51624T1 (de) | 1990-04-15 |
| NO855241L (no) | 1986-06-26 |
| KR930005332B1 (ko) | 1993-06-17 |
| NZ214676A (en) | 1988-06-30 |
| DK604485D0 (da) | 1985-12-23 |
| FI81576C (sv) | 1990-11-12 |
| KR860004892A (ko) | 1986-07-14 |
| EP0186525B1 (en) | 1990-04-04 |
| NO163957C (no) | 1990-08-15 |
| DE3576957D1 (de) | 1990-05-10 |
| JPS61275279A (ja) | 1986-12-05 |
| DK604485A (da) | 1986-06-26 |
| FI855128A (fi) | 1986-06-26 |
| PH25391A (en) | 1991-06-03 |
| ES550403A0 (es) | 1987-06-01 |
| AU575232B2 (en) | 1988-07-21 |
| AU5169985A (en) | 1986-07-03 |
| HUT39182A (en) | 1986-08-28 |
| US4740507A (en) | 1988-04-26 |
| FI855128A0 (fi) | 1985-12-20 |
| ES8706148A1 (es) | 1987-06-01 |
| ES8707535A1 (es) | 1987-08-01 |
| EP0186525A1 (en) | 1986-07-02 |
| IE58823B1 (en) | 1993-11-17 |
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Legal Events
| Date | Code | Title | Description |
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| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: SANKYO COMPANY LIMITED |